Human intelectin-1 (ITLN1) genetic variation and intestinal expression

Intelectins are ancient carbohydrate binding proteins, spanning chordate evolution and implicated in multiple human diseases. Previous GWAS have linked SNPs in ITLN1 (also known as omentin) with susceptibility to Crohn's disease (CD); however, analysis of possible functional significance of SNPs at this locus is lacking. Using the Ensembl database, pairwise linkage disequilibrium (LD) analyses indicated that several disease-associated SNPs at the ITLN1 locus, including SNPs in CD244 and Ly9, were in LD. The alleles comprising the risk haplotype are the major alleles in European (67%), but minor alleles in African superpopulations. Neither ITLN1 mRNA nor protein abundance in intestinal tissue, which we confirm as goblet-cell derived, was altered in the CD samples overall nor when samples were analyzed according to genotype. Moreover, the missense variant V109D does not influence ITLN1 glycan binding to the glycan beta -D-galactofuranose or protein-protein oligomerization. Taken together, our data are an important step in defining the role(s) of the CD-risk haplotype by determining that risk is unlikely to be due to changes in ITLN1 carbohydrate recognition, protein oligomerization, or expression levels in intestinal mucosa. Our findings suggest that the relationship between the genomic data and disease arises from changes in CD244 or Ly9 biology, differences in ITLN1 expression in other tissues, or an alteration in ITLN1 interaction with other proteins.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Immunologi inom det medicinska området hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Immunology in the medical area hsv//eng
genome-wide association
susceptibility loci
microbial glycans
alpha-defensins
crohns-disease
up-regulation
muc2 mucin
lectin
cells
recognition
Science & Technology - Other Topics

Castillo, P. A. (author)
Dugan, A. E. (author)
Almalki, F. (author)
Underwood, M. A. (author)
De La Motte, C. A. (author)
Yuan, W. (author)
Lu, W. (author)
Shen, B. (author)
Johansson, Malin E V,1971Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xjomal (author)
Kiessling, L. L. (author)
Hollox, E. J. (author)
Lonnerdal, B. (author)
Bevins, C. L. (author)
Göteborgs universitetInstitutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi (creator_code:org_t)

By the author/editor: Nonnecke, E. B.; Castillo, P. A.; Dugan, A. E.; Almalki, F.; Underwood, M. A.; De La Motte, C. ...; show more...; Yuan, W.; Lu, W.; Shen, B.; Johansson, Malin ...; Kiessling, L. L.; Hollox, E. J.; Lonnerdal, B.; Bevins, C. L.; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Immunology in th ...

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